Efficacy/Safety of Lefamulin in Severe Community-Acquired Bacterial Pneumonia

Pooled data from the LEAP 1 and 2 trials were used to study the efficacy and safety of lefamulin in patients with CABP at risk for severe pneumonia.

The following article features coverage from CHEST 2021, being held virtually from October 17 to October 20, 2021. Click here to read more of MPR‘s conference coverage.

To investigate the efficacy and safety of the pleuromutilin antibiotic lefamulin (LEF)  in patients with community-acquired bacterial pneumonia (CABP) who have or may be at risk for severe pneumonia, researchers analyzed pooled data from LEAP 1 and 2 clinical trials comparing LEF and moxifloxacin (MOX), analyzing the data based on the presence of unilobar vs multilobar infiltrates. Findings of this research were presented at the CHEST 2021 Annual Meeting, held live in Orlando, FL, and virtually, October 17 to 20.

The phase 3 LEAP 1 and 2 noninferiority trials (ClinicalTrials.gov Identifiers: NCT02559310 and NCT02813694, respectively) demonstrated a high level of efficacy for LEF in the treatment of adult patients with unilobar or multilobar pneumonia — a level comparable to that of moxifloxacin (MOX). The trials also showed both LEF and MOX had similar treatment-emergent adverse event (TEAE) profiles.  In LEAP 1, patients with CABP (Pneumonia Outcomes Research Team [PORT] risk class III to V; ≥25% required to have a PORT risk class of IV to V) received intravenous (IV) LEF 150 mg every 12 hours (q12h) for 5 to 7 days or MOX 400 mg every 24 hours (q24h) for 7 days, with an optional IV-to-oral switch available. In the LEAP 2 trial, patients with CABP (PORT risk class II to IV; ≥50% required to have a PORT risk class of III to IV) received oral LEF 600 mg q12h for 5 days  or MOX 400 mg q24h for 7 days.

In the current study, which focused specifically on patients with CABP who had or were at risk for severe pneumonia, investigators analyzed the microbiological intent-to-treat population (ie, all randomized patients with at least 1 CABP-causing baseline pathogen) looking at 1) early clinical response (ECR) at 96±24 hours after first study drug dose and 2) investigator assessment of clinical response (IACR) at test of cure (TOC; 5–10 days after last dose). TEAEs were also assessed.

In this post-hoc analysis, 343 patients were randomized to LEF and 333 were randomized to MOX. Among the total 676 randomized patients, 69% (468) had unilobar infiltrates and 31% (208) had multilobar infiltrates. Patients with multilobar pneumonia, compared with those with unilobar pneumonia, were more likely to be 65 years of age or older (47% vs 37%, respectively); have PORT] risk class of IV to V (25% vs 16%, respectively); or have a history of asthma/chronic obstructive pulmonary disease (21% vs 16%, respectively) or smoking (47% vs 41%, respectively).

The pathogen identified most often in both groups of participants was Streptococcus pneumonia — in at least 60% of individuals. Patients who received LEF or MOX exhibited high and similar ECR (unilobar pneumonia: LEF 92%, MOX 94%; multilobar pneumonia: LEF 85%, MOX 90%) and IACR success (unilobar pneumonia: LEF 86%, MOX 89%; multilobar pneumonia: LEF 77%, MOX 80%). The most frequently reported TEAEs were gastrointestinal, with similar rates of occurrence across the groups with LEF and MOX.

The researchers concluded that LEF is an alternative option to fluoroquinolones for the treatment of CABP in patients with multilobar pneumonia who either have or may be at risk for the development of severe pneumonia.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


File T, Mariano D, Gelone S, Moran G, Waterer G, Sandrock C. Lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia: pooled analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 trials in patients with multilobar or unilobar pneumonia. Presented at: CHEST 2021; October 17-20, 2021; Orlando, FL/Virtual. Abstract A522-A523.  

This article originally appeared on Pulmonology Advisor